EXCEED THE SPACE PROVIDED. Lung disease is a significant cause of mortality and morbidity in the United States. While all other major causes of death are decreasing, age-adjusted mortality due to lung disease continues to rise. The overall purpose of this COBRE renewal application is to continue the development of the research program in Lung Biology and Disease at The Vermont Lung Center (VLC) of the College of Medicine. The keystone of the VLC program is excellence. The scientific strengths include airway epithelial cell biology, cystic fibrosis, asthma inflammation, physiology, translational animal studies and clinical investigation into the pathogenesis of lung disease. In the last four years we have amassed a record of productivity including recruitment of a critical mass of well-trained PhD and MD pulmonary scientists, production of a large number of peer-reviewed publications, and increased extramural funding. A critical requirement for the continued success of the VLC is the stimulating environment in which optimal career development can occur. The goals of the VLC-COBRE are therefore to: 1) Train a group of talented MD and PhD biomedical investigators, 2) Provide career development and guidance through skilled mentoring, 3) Continue a stimulating, supportive, and "cutting edge" research milieu, 4) Maintain and expand the present critical mass of lung research-related investigators in Vermont. As support for these endeavors, we will continue to develop a state-of-the-art transgenic animal facility and augment the biomedical engineering research program at The University of Vermont. The VLC-COBRE will undertake 5 separate, but interrelated, research projects to build towards sustainability of the center. A particular focus of the present proposal on supporting and expanding translational multidisciplinary research. This addresses an urgent need because translational research allows basic advances in molecular, cellular and genetic science to be converted * into new methods of diagnosis and therapy. A critical mass of investigators has been recruited and will form the nexus for a future Program Project Grant application.